The prevalence of benign prostatic hyperplasia (BPH) increases sharply with age after 40 years, and by age 75 approximately 75% of men will have evidence of this disease. Despite intensive investigation, little is known about the molecular events that lead to BPH. At the histological level, it is clear that BPH arises from the transitional zone of the prostate, including either formation of nodules containing mostly stromal elements reminiscent of embryonic mesenchyme, or a mix of both stromal and epithelial elements with increased proliferation in one or both cellular compartments. This increased cell number leads to compression of the urethra, which can lead to problems with voiding and, in the worst case scenarios, renal dysfunction caused by bladder outlet obstruction (BOO).
Androgen signaling does not appear to be involved in initiation of the disease, however it is necessary for continued proliferation of the cells, and thus, pharmacological interventions for BPH include 5-alpha-reductase inhibitors to prevent the conversion of testosterone to dihydrotestosterone, reducing the benign prostatic enlargement (BPE). Patients are also typically treated with alpha-adrenergic antagonists, which release tension on the bladder neck, prostate, and prostatic capsule and therefore relieve BOO. Alpha-adrenergic antagonists are more effective as a short term treatment for BPH/lower urinary tract symptoms but over the long term, 5-alpha reductase inhibitors reduce the need for surgical intervention. Anti-androgens and gonadotropin-releasing hormone (GnRH) agonists may be more effective, but patients find the side-effects of androgen ablation unacceptable. In addition, treatment with alpha-1-adrenergic antagonists for BPH can be complicated by their hypotensive actions, in some cases leading to heart failure. Other side-effects of these treatments include asthenia (muscle weakness) and sudden falls in blood pressure resulting in dizziness. These side effects are bothersome enough to result in up to 10% of patients withdrawing from treatment. Reduction of the size of the prostate gland usually takes 6-12 months of treatment with 5-alpha-reductase inhibitors before symptoms are significantly improved.